학술논문
Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma
Document Type
Article
Author
Fischer, Luise; Grieb, Nora; Born, Patrick; Weiss, Ronald; Seiffert, Sabine; Boldt, Andreas; Fricke, Stephan; Franz, Paul; Heyn, Simone; Kubasch, Anne Sophie; Baber, Ronny; Weidner, Heike; Wang, Song Yau; Bach, Enrica; Hoffmann, Sandra; Ussmann, Jule; Kirchberg, Janine; Hell, Saskia; Schwind, Sebastian; Metzeler, Klaus H.; Herling, Marco; Jentzsch, Madlen; Franke, Georg-Nikolaus; Sack, Ulrich; Reiche, Kristin; Köhl, Ulrike; Platzbecker, Uwe; Vucinic, Vladan; Merz, Maximilian
Source
Leukemia; 20240101, Issue: Preprints p1-11, 11p
Subject
Language
ISSN
08876924; 14765551
Abstract
B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells. Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia. Our results show that in vivo expansion of CD8+CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients. In addition, our data provide evidence, that an increased fraction of CD8+T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome. We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion. Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented.